Biomedical subjects

Takahiro Shimizu

Publications and source records attributed to Takahiro Shimizu.

At least 19 recordsLinked to original sources

PubMed2006

Single-channel properties of volume-sensitive Cl- channel in ClC-3-deficient cardiomyocytes.

It is controversial whether the ClC-3 protein, which is one of the voltage-dependent chloride channel ClC family members, is a candidate for the volume-sensitive outwardly rectifying (VSOR) Cl(-) channel per se or its regulator. Here, for the first time, we examined the single-channel properties of the VSOR Cl(-) channel in ventricular myocytes isolated from ClC-3-deficient mice. The single-channel current induced by cell swelling exhibited Cl(-) selectivity, mild outward rectification, and an intermediate unitary conductance (around 38 pS). A Cl(-) channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), reversibly inhibited the outward current. These single-channel properties were identical with those in ClC-3 expressing wild-type ventricular myocytes. These results indicate that the single-channel activity of the VSOR Cl(-) channel is independent of the expression of ClC-3 proteins in mouse ventricular myocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2005

Brain phospholipase C/diacylglycerol lipase are involved in bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.

Bombesin receptors are mainly divided into two subtypes: BB1 receptor (neuromedin B-preferring receptor) and BB2 receptor [gastrin-releasing peptide (GRP)-preferring receptor]. Previously, we reported that intracerebroventricularly (i.c.v.) administered bombesin elevates plasma noradrenaline and adrenaline by production of brain arachidonic acid in rats. Arachidonic acid is released mainly by phospholipase A2 (PLA2)-dependent pathway or phospholipase C (PLC)/diacylglycerol lipase-dependent pathway. In the present study, bombesin and GRP elevated plasma catecholamines in a dose-dependent manner (1 and 5 nmol/animal, i.c.v.), while neuromedin B (1, 5 and 10 nmol/animal, i.c.v.) had no effect in urethane-anesthetized rats (bombesin=GRP>>neuromedin B). The bombesin (1 nmol/animal, i.c.v.)-induced response was dose-dependently attenuated by [D-Phe6, des-Met14]-bombesin (6-14) ethylamide (bombesin BB2 receptor antagonist) (15.3 and 30.6 nmol/animal, i.c.v.) and also by U-73122 (PLC inhibitor) (10 and 100 nmol/animal, i.c.v.) and RHC-80267 (diacylglycerol lipase inhibitor) (1.3 and 2.6 micromol/animal, i.c.v.). However, D-Nal-cyclo[Cys-Tyr-d-Trp-Orn-Val-Cys]-Nal-NH2 (bombesin BB1 receptor antagonist) (30 and 100 nmol/animal, i.c.v.), mepacrine (PLA2 inhibitor) (1.1 and 2.2 micromol/animal, i.c.v.) and U-73343 (inactive analog of U-73122) (100 nmol/animal, i.c.v.) had no effect. These results suggest the involvement of brain PLC/diacylglycerol lipase in the brain bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.

Adrenal Medulla↗

PubMed2005

Brain prostanoid TP receptor-mediated adrenal noradrenaline secretion and EP3 receptor-mediated sympathetic noradrenaline release in rats.

Sympathetic nerves release noradrenaline, whereas adrenal medullary chromaffin cells secrete noradrenaline and adrenaline. Therefore, plasma noradrenaline reflects the secretion from adrenal medulla in addition to the release from sympathetic nerves, however the exact mechanisms of adrenal noradrenaline secretion remain to be elucidated. The present study was designated to characterize the source of plasma noradrenaline induced by intracerebroventricularly (i.c.v.) administered bombesin and prostaglandin E2 in urethane-anesthetized rats. Bombesin (1.0 nmol/animal, i.c.v.) elevated plasma noradrenaline and adrenaline, while prostaglandin E2 (0.3 nmol/animal, i.c.v.) elevated only plasma noradrenaline. The bombesin-induced elevations of both catecholamines were attenuated by pretreatments with furegrelate (an inhibitor of thromboxane A2 synthase) [250 and 500 microg (0.9 and 1.8 micromol)/animal, i.c.v.)] and [(+)-S-145] [(+)-(1R,2R,3S,4S)-(5Z)-7-(3-[4-3H]-phenylsulphonyl-aminobicyclo[2.2.1]hept-2-yl)hept-5-enoic acid sodium salt] (an antagonist of prostanoid TP receptors) [100 and 250 microg (250 and 625 nmol)/animal)], and abolished by acute bilateral adrenalectomy. On the other hand, the prostaglandin E2-induced elevation of plasma noradrenaline was not influenced by acute bilateral adrenalectomy. These results suggest that adrenal noradrenaline secretion and sympathetic noradrenaline release are mediated by differential central mechanisms; brain prostanoid TP receptors activated by bombesin are involved in the adrenal noradrenaline secretion, while brain prostanoid EP (probably EP3) receptors activated by prostaglandin E2 are involved in the sympathetic noradrenaline release in rats. Brain prostanoid TP receptors activated by bombesin are also involved in the adrenal adrenaline secretion.

Adrenal Glands↗

PubMed2005

Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine.

Long-acting dihydropyridine calcium channel blockades have been shown to limit the progression of atherosclerosis and decrease the incidence of cardiovascular events in humans and animals. To investigate the vasoprotective effects beyond the blood pressure-lowering effects of these agents, amlodipine (20 mg/kg/ day) and manidipine (10 mg/kg/day) were administered by gavage to N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats for 2 weeks. L-NAME treatment (0.7 mg/ml in drinking water) significantly decreased the gene and protein expression of endothelial nitric oxide synthase (eNOS) and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) mRNA levels in the aorta, as determined by Western blotting and reverse transcription (RT)-polymerase chain reaction (PCR). Amlodipine and manidipine normalized the decreased expression of eNOS gene and protein, and attenuated the overexpression of NADPH oxidase, VCAM-1, and MCP-1 mRNA. Furthermore, amlodipine and manidipine prevented the L-NAME-induced increase in the angiotensin converting enzyme (ACE) mRNA content, thereby restoring control levels in the aorta. On the other hand, hydralazine treatment had no such effect in L-NAME treated rats. Furthermore, the increased expression of manganese superoxide dismutase (Mn-SOD) by L-NAME treatment was not affected by amlodipine, manidipine, or hydralazine. We concluded that the direct anti-inflammatory and antioxidative effects of calcium channel blockades in the aorta of rats with L-NAME-induced hypertension were not likely to have been mediated by the blood pressure-lowering action of these agents, but instead these beneficial effects appear to have been mediated by an augmentation of eNOS expression and by the inhibition of the expression of ACE.

Amlodipine↗

PubMed2004

Role of K+ channels in M2 muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach.

Previously we reported the cholinergic M2 muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach (K. Yokotani, Y. Osumi. J Pharmacol Exp Ther. 1993;264:54-60). In the present study, we investigated the role of K+ channels in oxotremorine (a muscarinic receptor agonist)-induced inhibition of noradrenaline release using isolated, vascularly perfused rat stomach. The gastric postganglionic sympathetic nerves were electrically stimulated twice at 2.5 Hz for 1 min and test reagents were added during the second stimulation. The electrically evoked release of noradrenaline was augmented by tetraethylammonium and 4-aminopyridine (non-selective K+ channel blockers) and also by charybdotoxin (a blocker of big conductance Ca2+-activated K+ channel). On the other hand, apamin (a selective blocker of small conductance Ca2+-activated K+ channels) and glibenclamide (an ATP-activated K+ channel blocker) had no effect on the evoked noradrenaline release. Oxotremorine-induced inhibition of noradrenaline release was attenuated by tetraethylammonium and 4-aminopyridine, while the inhibition was not influenced by charybdotoxin, apamin, and glibenclamide. These results suggest that tetraethylammonium- and 4-aminopyridine-sensitive K+ channels (probably voltage-activated K+ channels) are involved in the muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach.

Animals↗

PubMed2004

Brain phospholipase C-diacylglycerol lipase pathway is involved in vasopressin-induced release of noradrenaline and adrenaline from adrenal medulla in rats.

Recently, we reported that intracerebroventricularly (i.c.v.) administered arginine-vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by brain thromboxane A2-mediated mechanisms in rats. These results suggest the involvement of brain arachidonic acid in the vasopressin-induced activation of the central adrenomedullary outflow. Arachidonic acid is released mainly by two pathways: phospholipase A2 (PLA2)-dependent pathway; phospholipase C (PLC)- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we attempted to identify which pathway is involved in the vasopressin-induced release of both catecholamines from adrenal medulla using urethane-anesthetized rats. Vasopressin (0.2 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was dose-dependently reduced by neomycin [0.28 and 0.55 micromol (250 and 500 microg)/animal, i.c.v.] and 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) [5 and 10 nmol (2.3 and 4.6 microg)/animal, i.c.v.] (inhibitors of PLC), and also by 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) [1.3 and 2.6 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 and 2.2 micromol (500 and 1000 microg)/animal, i.c.v.] (an inhibitor of PLA2) was largely ineffective on the vasopressin-induced elevation of plasma catecholamines. These results suggest that vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by the brain PLC- and diacylglycerol lipase-dependent mechanisms in rats.

Adrenal Medulla↗

PubMed2004

Regulatory volume increase after secretory volume decrease in colonic epithelial cells under muscarinic stimulation.

To address the question of whether colonic secretory cells change their volume in response to carbachol (CCh) stimulation and, if so, the mechanisms involved therein, we used two-photon laser scanning microscopy to measure the volume of individual epithelial cells in the fundus region of crypts isolated from the guinea-pig distal colon. We also measured the volume of human colonic epithelial T84 cells using an electronic sizing technique. Both types of colonocytes responded to stimulation by CCh with shrinkage and then underwent a regulatory volume increase (RVI), even during continued stimulation by CCh. The secretory volume decrease (SVD) induced by CCh was antagonized by atropine, BAPTA loading and niflumic acid, a blocker of Ca(2+)-activated Cl(-) channels. An increase in the intracellular free [Ca(2+)] was observed with fura-2 during these volume responses to CCh. Removal of all Na(+) or K(+) or of most of the Cl(-) from the extracellular solution abolished the RVI, but not the preceding SVD. The RVI, but not the preceding SVD, was abolished by bumetanide, a blocker of the Na(+)-K(+)-2Cl(-) cotransporter. We conclude that guinea-pig crypt colonocytes and human T84 cells exhibit a cytosolic Ca(2+)-dependent SVD and undergo a subsequent RVI that is dependent on the operation of Na(+)-K(+)-2Cl(-) cotransporters.

Animals↗

PubMed2004

Dual roles of plasmalemmal chloride channels in induction of cell death.

Even under anisotonic conditions, most cells can regulate their volume by mechanisms called regulatory volume decrease (RVD) and increase (RVI) after osmotic swelling or shrinkage, respectively. In contrast, the initial processes of necrosis and apoptosis are associated with persistent swelling and shrinkage. Necrotic volume increase (NVI) is initiated by uptake of osmolytes, such as Na+, Cl- and lactate, under conditions of injury, hypoxia, ischaemia, acidosis or lactacidosis. Persistence of NVI is caused by dysfunction of RVD due to impairment of volume-sensitive Cl- channels under conditions of ATP deficiency or lactacidosis. Both lactacidosis-induced RVD dysfunction and necrotic cell death are prevented by pretreatment of cells with the vacuolating cytotoxin-A (VacA) toxin protein purified from Helicobacter pylori, which forms a lactacidosis-resistant anion channel. Apoptotic volume decrease (AVD) is triggered by activation of K+ and Cl- conductances following stimulation with a mitochondrion-mediated or death receptor-mediated apoptosis inducer. Apoptotic cell death can be prevented by blocking the Cl- channels but not the K+-Cl- cotransporters. Thus, the volume regulatory anion channel plays, unless impaired, a cell-rescuing role in the necrotic process by ensuring RVD after swelling induced by necrotic insults, whereas normotonic activation of the anion channel plays a cell-killing role in the apoptotic process by triggering AVD following stimulation with apoptosis inducers.

Animals↗

PubMed2004

A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl(-) channel.

Apoptotic volume decrease is a pivotal event triggering a cell to undergo apoptosis and is induced by ionic effluxes resulting mainly from increased K(+) and Cl(-) conductances. Here, we demonstrate that in human epithelia HeLa cells both mitochondrion- and death receptor-mediated apoptosis inducers [staurosporine and Fas ligand or tumor necrosis factor (TNF)-alpha] rapidly activate Cl(-) currents that show properties phenotypical of volume-sensitive outwardly rectifying Cl(-) channel currents, including outward rectification, voltage-dependent inactivation gating at large positive potentials, inhibition by osmotic shrinkage, sensitivity to classic Cl(-) channel blockers, and dependence on cytosolic ATP. Staurosporine, but not Fas ligand or TNF-alpha, rapidly (within 30 min) increased the intracellular level of reactive oxygen species (ROS). A ROS scavenger and an NAD(P)H oxidase inhibitor blocked the current activation by staurosporine but not by Fas ligand or TNF-alpha. A ROS scavenger also inhibited apoptotic volume decrease, caspase-3 activation, and apoptotic cell death induced by staurosporine. Thus, it is concluded that an apoptosis-triggering anion conductance is carried by the volume-sensitive outwardly rectifying Cl(-) channel and that the channel activation on apoptotic stimulation with staurosporine, but not with Fas ligand or TNF-alpha, is mediated by ROS.

Apoptosis↗

PubMed2004

Expression of novel isoforms of the CIC-1 chloride channel in astrocytic glial cells in vitro.

Chloride channels play an important role in glial astrocyte function. However, in astrocytes, no chloride channels besides the gamma-aminobutyric acid (GABA)A receptor, glycine receptor, and ClC-2 chloride channels have been molecularly identified. In this study, we examined the expression of the ClC-1 chloride channel in rat astrocytic glioma C6 cells and rat primary astrocytes. Five isoforms of ClC-1, but not skeletal muscle ClC-1 (SM ClC-1), were found to be expressed in C6 cells. Comparison with rat SM ClC-1 showed that common features shared by these isoforms are a short 3' end with a deletion of the nucleotides from 3115 to 3197 and a substitution of T by C at nucleotides 480 and 1733. Three of the five isoforms, M1, M2, and M3, were produced by partial deletion of ClC-1 exon 7, partial insertion of ClC-1 exon 7a, and a TAG insertion at nucleotide 858, respectively. One of the two remaining isoforms, M4, was produced by partial deletion of ClC-1 exon 8 at nucleotide 937; the other, M5, was the same as SM ClC-1 except for the short 3' end and substitutions at the two positions. Only the M5 isoform could be expressed as a functional channel in Xenopus oocytes. This glial isoform exhibited less dependence on voltage and extracellular Cl- than rat SM ClC-1. However, the anion selectivity sequence and the anthracene-9-carboxylic acid (9-AC) sensitivity of this channel were the same as for SM ClC-1. Since whole-cell recordings failed to detect ClC-1-like Cl- currents in C6 cells, it appears that the ClC-1 isoform is functioning in intracellular organelles. In rat primary astrocytes, we found that the M2 isoform as well as two additional distinct isoforms were expressed. The present study showed that astrocytic glial cells express multiple isoforms of the ClC-1 chloride channel, which has been thought to be expressed almost exclusively in the skeletal muscle.

Animals↗

PubMed2004

Histological and immunohistochemical observations of mucin-depleted foci (MDF) stained with Alcian blue, in rat colon carcinogenesis induced with 1,2-dimethylhydrazine dihydrochloride.

The usefulness of mucin-depleted foci (MDF), which have recently been proposed as a new preneoplastic biomarker in rat colon carcinogenesis, was histologically investigated in rat colonic tissues treated with 1,2-dimethylhydrazine dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and beta-catenin accumulated crypts (BCAC) was examined by comparing the corresponding computer-captured images. Twelve male F344 rats were given DMH s.c. at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided into two groups. Rats in group 1 were given normal drinking water, while those in group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6 weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The resected colons were fixed in 10% formalin, and stained with Alcian blue for observation of ACF and MDF. Histological and immunohistochemical analysis revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated with IND) were significantly decreased, compared with those in group 1. The number of BCAC in group 2 was also significantly lower than that in group 1. The reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF. Analyses of the computer-captured images indicated that MDF had more frequent dysplastic changes and overexpression of beta-catenin than did ACF. MDF having over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These results suggest that MDF may be useful as an early biomarker in colon carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed2004

Possible involvement of pyruvate kinase in acquisition of tolerance to hypoxic stress in glial cells.

Neurons are highly vulnerable to ischemic/hypoxic stress, while glial cells show tolerance to such stress. However, the mechanisms for tolerance acquisition in glial cells have yet to be established. We attempted to isolate and identify a stress protein that is upregulated in response to hypoxia in human astrocytoma CCF-STTG1 cells. In particular, pyruvate kinase (PK) was upregulated by hypoxia in CCF-STTG1 cells. Hypoxia-inducible factor 1 (HIF-1), the primary transcription factor that is responsible for multiple gene activation under hypoxia, plays a critical role in PK expression during hypoxic challenge. To determine whether newly synthesized PK is involved in tolerance to hypoxic stress, we established the PK-overexpressing neuronal cells. Overexpression of the wild-type, but not the kinase-negative mutant, resulted in attenuation of the loss of cell viability and the typical apoptotic features by hypoxia or oxidative stress in SK-N-MC cells. These findings suggest that upregulation of PK may result in acquisition of tolerance against hypoxic stress, and that the antioxidant effect may be involved in the protective effect of PK.

Antimutagenic Agents↗

PubMed2004

ClC-3-independent, PKC-dependent activity of volume-sensitive Cl channel in mouse ventricular cardiomyocytes.

Volume-sensitive outwardly rectifying (VSOR) Cl- channels are activated during osmotic swelling and involved in the subsequent volume regulation in most animal cells. To test the hypothesis that the ClC-3 protein is the molecular entity corresponding to the VSOR Cl- channel in cardiomyocytes, the properties of VSOR Cl- currents in single ventricular myocytes isolated from ClC-3-deficient (Clcn3(-/-)) mice were compared with those of the same currents in ClC-3-expressing wild-type (Clcn3(+/+)) and heterozygous (Clcn3(+/-)) mice. Basal whole-cell currents recorded under isotonic conditions in ClC-3-deficient and -expressing cells were indistinguishable. The biophysical and pharmacological properties of whole-cell VSOR Cl- currents in ClC-3-deficient cells were identical in ClC-3-expressing cells. The VSOR Cl- current density, which is an indicator of the plasmalemmal expression of functional channels, was essentially the same in cells isolated from these 3 types of mice and C57BL/6 mice. Activation of protein kinase C (PKC) by a phorbol ester was found to upregulate VSOR Cl- currents in ClC-3-deficient and -expressing cardiomyocytes. This effect is opposite to the reported downregulatory effect of PKC activators on ClC-3-associated Cl- currents. We thus conclude that functional expression of VSOR Cl- channels in the plasma membrane of mouse cardiomyocytes is independent of the molecular expression of ClC-3.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2003

Hypertonic activation of a non-selective cation conductance in HeLa cells and its contribution to cell volume regulation.

In whole-cell recordings on single HeLa cells, the hypertonic activation of a cation conductance with a selectivity ratio P(Na):P(Li):P(K):P(Cs):P(NMDG):P(Ca):P(Cl) of 1.00:0.86:0.84:0.56:0.10:0.07:0.15 was observed. This (non-selective) cation conductance was reduced to 59 and 30% of maximal stimulation by Gd(3+) and flufenamate, respectively, but it was insensitive to amiloride (with each compound applied at 100 microm/l). As was determined by the Coulter counter technique, the cation conductance was the main mechanism of regulatory volume increase (RVI) in HeLa cells. Whereas a significant contribution of Na(+)/H(+) antiport was also detectable, Na(+)-K(+)-2Cl(-) symport most likely did not contribute to RVI.

Cations↗

PubMed2003

Brain phospholipase C and diacylglycerol lipase are involved in corticotropin-releasing hormone-induced sympatho-adrenomedullary outflow in rats.

Previously, we reported that the elevation of plasma noradrenaline and adrenaline induced by intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) was abolished by i.c.v. administered indomethacin, an inhibitor of cyclooxygenase, in rats [Yokotani et al., Eur. J. Pharmacol. 419, 183-189, 2001]. The result suggests the involvement of active metabolites of brain arachidonic acid in the CRH-induced activation of the central sympatho-adrenomedullary outflow. Arachidonic acid is released mainly by two different pathways: phospholipase A2-dependent pathway; phospholipase C- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we tried to identify which pathway is involved in the CRH-induced elevation of plasma catecholamines in urethane-anesthetized rats. CRH (1.5 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was abolished by neomycin [0.55 micromol (500 microg)/animal, i.c.v.] and 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U-73122) [5 nmol (2.3 microg)/animal, i.c.v.] (inhibitors of phospholipase C), and also by 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267) [1.3 micromol (500 microg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 micromol (500 microg)/animal, i.c.v.] (an inhibitor of phospholipase A2) and 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-2,5-pyrrolidinedione (U-73343) [5 nmol (2.3 microg)/animal, i.c.v.] (an inactive analog of U-73122) had no effect. These results suggest that CRH activates the central sympatho-adrenomedullary outflow by the brain phospholipase C- and diacylglycerol lipase-dependent mechanisms in rats.

Adrenal Medulla↗

PubMed2003

Extrahypothalamic corticotropin-releasing hormone mediates (-)-nicotine-induced elevation of plasma corticosterone in rats.

(-)-Nicotine activates the hypothalamic-pituitary-adrenal axis via an activation of the brainstem catecholaminergic neurons in rats. The present study was undertaken to clarify the mechanisms involved in the (-)-nicotine-induced activation of brainstem catecholaminergic neurons in anesthetized rats. Physostigmine (a cholinesterase inhibitor) (0.31 and 0.77 micromol/animal, i.p.) dose-dependently elevated plasma corticosterone in the presence of scopolamine (a muscarinic receptor antagonist) (2.3 micromol/animal, i.p.). (-)-Nicotine (250 and 500 nmol/animal, i.c.v.) dose-dependently elevated plasma corticosterone with concomitant noradrenaline release in the hypothalamic paraventricular nucleus. The (-)-nicotine (500 nmol/animal, i.c.v.)-induced elevation of corticosterone was abolished by phentolamine (an alpha-adrenoceptor antagonist) (0.66 micromol/animal, i.c.v.), and attenuated by (+/-)-sotalol (a beta-adrenoceptor antagonist) (0.97 micromol/animal, i.c.v.). The (-)-nicotine-induced increases of plasma corticosterone and hypothalamic noradrenaline release were abolished either by hexamethonium (a nicotinic acetylcholine receptor antagonist) (1.8 micromol/animal, i.c.v.), CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) (a selective CRF-1 receptor antagonist) (1.3 micromol/animal, i.c.v.) or indomethacin (a cyclooxygenase inhibitor) (1.2 micromol/animal, i.c.v.). These results suggest that (-)-nicotine elevates plasma corticosterone by CRF-1 receptor- and prostaglandin-mediated noradrenaline release in the paraventricular nucleus in rats.

Animals↗

PubMed2003

Analysis of the effect of foreign gases in the production of hyperpolarized 129Xe gas on a simple system working under atmospheric pressure.

Experimental conditions that affect the degree of polarization of 129Xe gas were tested for a higher degree of polarization to facilitate a laboratory use of 129Xe NMR, primarily on the effect of addition of foreign gases. When He, N(2), or D(2) gas was added separately to pure Xe gas with natural isotope abundance, D(2) gas gave better results than the others in enhancing the degree of polarization in 129Xe atom. When these gases were added in mixture, however, N(2) plus He was proved to be more efficient than D(2) or He in enhancing the degree of polarization. As a result, the degree of polarization was found to be increased by more than an order, when diluent gases were properly mixed; polarization as high as 35% was reached at gas composition of 5% Xe, 10% N(2), and 85% He, whereas only a few percent was attainable when Xe gas was polarized without mixing any foreign gases [J. Magn. Reson. 150 (2), 156-160 (2001)]. These results were discussed on a basis of quenching and buffer effects of foreign gases. Polarization was also measured after separating the pure Xe gas from the mixture; value of 22% was obtained for the Xe gas isolated after solidification in liquid nitrogen trap. Build-up time of the polarization was also tested, which did not change remarkably depending on the gas composition.

Journal Article↗

PubMed2003

Development of the overt-covert aggression inventory.

The expression of anger in Japanese people is different from that of other races. We developed a new brief inventory, the Overt-Covert Aggression Inventory, to assess aggressive behavior ofJapanese people by focusing on their uniqueness and examined its reliability and validity. This inventory, the Center for Epidemiological Studies Depression scale, the Japanese version of the Buss-Perry Aggression Questionnaire, and the Picture-Frustration Study were administered to 3,104 men and 316 women in a factory. Internal consistency, test-retest reliability, concurrent validity, and construct validity of the scale were examined. We confirmed that the Overt-Covert Aggression Inventory has adequate reliability and sufficient concurrent validity, however, further studies of the construct validity and discriminant validity are required.

Adult↗